Exosomal miR-590-3p derived from cancer-associated fibroblasts confers radioresistance in colorectal cancer

Chen, Xijuan; Liu, Yingqiang; Zhang, Qinglan; Liu, Baoxing; Cheng, Yan; Zhang, Yonglei; Sun, Yanan; Liu, Junqi

doi:10.1016/j.omtn.2020.11.003

Cited by 73 publications

(61 citation statements)

References 45 publications

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“…In CRC, the CAFs-derived exosomes have been reported as an important cause of radio resistance of cancer cells by preventing the DNA damage and inhibiting apoptosis and in CRC cells. These results were associated with reduced activities of cleaved-caspase 3 and cleavedpoly (ADP-Ribose) polymerase 1 (PARP) induced by CAFs-derived exosomes [139]. The up-regulated miR-590-3p in CAFs-derived exosomes compared with normal fibroblast-derived exosomes was confirmed to play a critical role in this regulation by targeting at chloride channel accessory 4 (CLCA4) and activating the PI3K/ AKT signaling pathway [139].…”

Section: Therapy Resistancementioning

confidence: 96%

Cancer associated-fibroblast-derived exosomes in cancer progression

et al. 2021

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To identify novel cancer therapies, the tumor microenvironment (TME) has received a lot of attention in recent years in particular with the advent of clinical successes achieved by targeting immune checkpoint inhibitors (ICIs). The TME consists of multiple cell types that are embedded in the extracellular matrix (ECM), including immune cells, endothelial cells and cancer associated fibroblasts (CAFs), which communicate with cancer cells and each other during tumor progression. CAFs are a dominant and heterogeneous cell type within the TME with a pivotal role in controlling cancer cell invasion and metastasis, immune evasion, angiogenesis and chemotherapy resistance. CAFs mediate their effects in part by remodeling the ECM and by secreting soluble factors and extracellular vesicles. Exosomes are a subtype of extracellular vesicles (EVs), which contain various biomolecules such as nucleic acids, lipids, and proteins. The biomolecules in exosomes can be transmitted from one to another cell, and thereby affect the behavior of the receiving cell. As exosomes are also present in circulation, their contents can also be explored as biomarkers for the diagnosis and prognosis of cancer patients. In this review, we concentrate on the role of CAFs-derived exosomes in the communication between CAFs and cancer cells and other cells of the TME. First, we introduce the multiple roles of CAFs in tumorigenesis. Thereafter, we discuss the ways CAFs communicate with cancer cells and interplay with other cells of the TME, and focus in particular on the role of exosomes. Then, we elaborate on the mechanisms by which CAFs-derived exosomes contribute to cancer progression, as well as and the clinical impact of exosomes. We conclude by discussing aspects of exosomes that deserve further investigation, including emerging insights into making treatment with immune checkpoint inhibitor blockade more efficient.

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Section: Therapy Resistancementioning

confidence: 96%

Cancer associated-fibroblast-derived exosomes in cancer progression

et al. 2021

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“…A recent finding has discovered that cetuximab increases CAFs' EGF secretion, which is sufficient to render neighboring cancer cells resistant to cetuximab in combination with chemotherapy for metastatic CRC patients (Garvey et al, 2020). Moreover, CAFderived exosomal miR-93-5p or miR-590-3p has been shown to rescue CRC cells from radiation-induced apoptosis (Chen et al, 2020(Chen et al, , 2021, and the promoted CRC stemness was demonstrated to account for the radioresistance imposed by CAF-derived exosomes . Thus, these discoveries build a mechanistic connection between CAF-maintained cancer stemness and therapy resistance in CRC.…”

Section: Stemness and Therapy Resistancementioning

confidence: 99%

The Versatile Roles of Cancer-Associated Fibroblasts in Colorectal Cancer and Therapeutic Implications

Deng

Jiang

Zeng

et al. 2021

Front. Cell Dev. Biol.

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The tumor microenvironment (TME) is populated by abundant cancer-associated fibroblasts (CAFs) that radically influence the disease progression across many cancers, including the colorectal cancer (CRC). In theory, targeting CAFs holds great potential in optimizing CRC treatment. However, attempts to translate the therapeutic benefit of CAFs into clinic practice face many obstacles, largely due to our limited understanding of the heterogeneity in their origins, functions, and mechanisms. In recent years, accumulating evidence has uncovered some cellular precursors and molecular markers of CAFs and also revealed their versatility in impacting various hallmarks of CRC, together helping us to better define the population of CAFs and also paving the way toward their future therapeutic targeting for CRC treatment. In this review, we outline the emerging concept of CAFs in CRC, with an emphasis on their origins, biomarkers, prognostic significance, as well as their functional roles and underlying mechanisms in CRC biology. At last, we discuss the prospect of harnessing CAFs as promising therapeutic targets for the treatment of patients with CRC.

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“…AZGP1 is a useful diagnostic biomarker found in the tissues and serum of Chinese CRC patients and it promotes epithelial-mesenchymal transition (EMT) in colorectal cancer via the filamin A-mediated focal adhesion pathway [44]. Furthermore, other genes associated with MC1R in the PPI, such as MMP7, CLCA4, MS4A12, KRT23, and NFE2L3, have been shown to play a vital role in the progression of CRC [45][46][47][48][49]. Overall, MC1R may be involved in the occurrence and development of CRC by interacting with the above molecules.…”

Section: Discussionmentioning

confidence: 99%

MC1R Is a Prognostic Marker and Its Expression Is Correlated with MSI in Colorectal Cancer

Peng

Chang

et al. 2021

CIMB

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Melanocortin 1 receptor (MC1R) is thought to be a marker of poor prognosis and a potential target for the treatment of melanoma. Studies have found that MC1R promotes several tumor behaviors, including cell proliferation and differentiation, pigment formation, and genome damage repair. Some single-nucleotide polymorphisms (SNPs) of MC1R are involved in the occurrence and development of melanoma. A few studies have reported a relationship between MC1R and colorectal cancer (CRC). In this research, our objective was to examine MC1R expression and MC1R SNPs and investigate their correlation with the clinicopathological features of human CRC tissues. We evaluated MC1R mRNA expression by performing bioinformatic analyses on human CRC expression datasets. We used Western blotting and RT-qPCR to compare MC1R expression in CRC tissues with that in normal tissues, and MC1R SNPs in CRC tissues were detected by PCR-direct sequencing (DS). The expression of MC1R was significantly decreased in CRC tissues compared with normal tissue, and its expression was negatively associated with P53 expression, MLH1 expression, and PMS2 expression, and high MC1R expression was significantly associated with microsatellite instability (MSI). MC1R SNPs were also associated with the clinicopathological characteristics of CRC; for example, the rs2228479 locus genotype was correlated with Ki67 status, and the rs885479 locus genotype was correlated with age and T stage. In conclusion, MC1R plays a crucial role in the progression of CRC and may be a marker of poor prognosis in CRC.

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Exosomal miR-590-3p derived from cancer-associated fibroblasts confers radioresistance in colorectal cancer

Cited by 73 publications

References 45 publications

Cancer associated-fibroblast-derived exosomes in cancer progression

Cancer associated-fibroblast-derived exosomes in cancer progression

The Versatile Roles of Cancer-Associated Fibroblasts in Colorectal Cancer and Therapeutic Implications

MC1R Is a Prognostic Marker and Its Expression Is Correlated with MSI in Colorectal Cancer

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